Recovered versus preserved ejection fraction in heart failure: long-term outcomes and the role of sustained remission
E Tartaglia, T Bucci, M Rossi, L Serio, A Askarinejad, G Boriani, G Y H LipAbstract
Background
Heart failure (HF) is traditionally classified according to left ventricular ejection fraction (LVEF), a dynamic measure that may change over time. Although guidelines recognize HF with recovered LVEF, its long-term risk compared with preserved LVEF remains uncertain.
Purpose
To evaluate the long-term risk of adverse outcomes in patients with HF and recovered ejection fraction (HFrecEF) compared with those with preserved ejection fraction (HFpEF), and to assess the prognostic impact of sustained remission defined by one- and two-year stability of LVEF recovery.
Methods
A retrospective cohort study using data from a global federated network (TriNetX). Adult patients (≥18 years) diagnosed with HF between 2018 and 2023 were identified and categorized according to longitudinal LVEF patterns. HFrecEF was defined as prior LVEF ≤40% followed by an absolute increase of ≥10 percentage points and subsequent recovery to LVEF ≥50%. HFpEF was defined as preserved LVEF (≥50%) without prior evidence of reduced LVEF. HF with remission of ejection fraction (HFremEF) was defined as HFrecEF with a sustained maintenance of LVEF ≥50% for one or two years. The primary outcome was a composite of all-cause mortality or acute decompensated HF. Secondary outcomes included its individual components. Exploratory outcomes were new-onset atrial fibrillation and ventricular arrhythmias. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models after 1:1 propensity score matching.
Results
We identified 6,590 patients with HFrecEF (age 64.3 ± 12.5 years, 42.0% females) and 585,858 patients with HFpEF (72.2 ± 12.9 years, 56.9% females). Before propensity score matching, HFrecEF patients were younger, less frequently female, and exhibited a higher burden of cardiovascular comorbidities and greater use of HF-related therapies compared with HFpEF patients. After matching, 6,535 pairs were analyzed. Compared with HFpEF, HFrecEF was associated with a lower risk of the composite outcome (HR 0.87, 95% CI 0.83–0.91), with lower risks of all-cause mortality (HR 0.77, 95% CI 0.73–0.82) and acute decompensated HF (HR 0.94, 95% CI 0.89–0.99) (Figure 1; Figure 2). HFrecEF was also associated with a lower risk of new-onset atrial fibrillation (HR 0.87, 95% CI 0.83–0.92), but a higher risk of ventricular arrhythmias (HR 1.58, 95% CI 1.45–1.73) (Figure 2). Results were consistent in HFremEF, with both one- and two-year remission showing a similarly lower risk of the composite outcome compared with HFpEF (HR 0.87, 95% CI 0.82–0.92 and HR 0.88, 95% CI 0.83–0.94, respectively), with a concordant pattern across secondary and exploratory outcomes.
Conclusion
HFrecEF patients are at lower risk of adverse events compared with HFpEF patients. These findings suggest that similar LVEF does not imply similar prognosis, underscoring HF as a dynamic condition beyond static ejection fraction–based categories.